Eupatilin alleviates airway remodeling via regulating phenotype plasticity of airway smooth muscle cells

Li, Yanqi; Ren, Rong; Wang, Lijun; Peng, Kan

doi:10.1042/bsr20191445

Cited by 8 publications

(9 citation statements)

References 26 publications

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“…24 Besides, by inhibiting STAT3, Eupatilin attenuates airway remodeling and inhibits gastric cancer cell growth. 25,26 A recent study has shown that Eupatilin is associated with coagulation. It can inhibit arachidonic acid (AA)-induced platelet aggregation and thromboxane A2 (TXA2) and 5-hydroxytryptophan (5-HT) generation.…”

Section: Introductionmentioning

confidence: 99%

Pretreatment with Eupatilin Attenuates Inflammation and Coagulation in Sepsis by Suppressing JAK2/STAT3 Signaling Pathway

Lu¹,

Li²,

Huang³

et al. 2023

JIR

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Sepsis is an aggressive and life-threatening organ dysfunction induced by infection. Excessive inflammation and coagulation contribute to the negative outcomes for sepsis, resulting in high morbidity and mortality. In this study, we explored whether Eupatilin could alleviate lung injury, reduce inflammation and coagulation during sepsis. Methods: We constructed an in vitro sepsis model by stimulating RAW264.7 cells with 1 μg/mL lipopolysaccharide (LPS) for 6 hours. The cells were divided into control group, LPS group, LPS+ Eupatilin (Eup) group, and Eup group to detect their cell activity and inflammatory cytokines and coagulation factor levels. Cells in LPS+Eup and Eup group were pretreated with Eupatilin (10μM) for 2 hours. In vivo, mice were divided into sham operation group, cecal ligation and puncture (CLP) group and Eup group. Mice in the CLP and Eup groups were pretreated with Eupatilin (10mg/kg) for 2 hours by gavage. Lung tissue and plasma were collected and inflammatory cytokines, coagulation factors and signaling were measured. Results: In vitro, tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6, and tissue factor (TF) expression in LPS-stimulated RAW264.7 cells was downregulated by Eupatilin (10μM). Furthermore, Eupatilin inhibited phosphorylation of the JAK2/STAT3 signaling pathway and suppressed p-STAT3 nuclear translocation. In vivo, Eupatilin increased the survival rate of the mice. In septic mice, plasma concentrations of TNF-α, IL-1β and IL-6, as well as TF, plasminogen activator inhibitor 1 (PAI-1), D-dimer, thrombinantithrombin complex (TAT) and fibrinogen were improved by Eupatilin. Moreover, Eupatilin alleviated lung injury by improving the expression of inflammatory cytokines and TF, fibrin deposition and macrophage infiltration in lung tissue. Conclusion:Our results revealed that Eupatilin may modulate inflammation and coagulation indicators as well as improve lung injury in sepsis via the JAK2/STAT3 signaling pathway.

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Section: Introductionmentioning

confidence: 99%

Pretreatment with Eupatilin Attenuates Inflammation and Coagulation in Sepsis by Suppressing JAK2/STAT3 Signaling Pathway

Lu¹,

Li²,

Huang³

et al. 2023

JIR

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“…The review also presents the anti-inflammatory properties of eupatilin against various disease models and its molecular targets, antioxidant activity through different molecular mechanisms, and neuroprotective activity both in vitro and in vivo. In 2020, Li et al [ 200 ] conducted an in vitro experiment that showed that compound 89 suppressed the proliferation and migration of airway smooth muscle cells (ASMCs). Exposure of ASMCs to eupatilin increased the expression of contractile markers smooth muscle, whereas the expression of extracellular matrix (ECM) proteins, type I collagen (Coll I), and fibronectin were reduced; the activation of nuclear factor κB (NF-κB), signal transducer and activator of transcription 3 (STAT3), and AKT pathways caused by TGF-β1 in ASMCs was present.…”

Section: Biological Activitymentioning

confidence: 99%

Stevia Genus: Phytochemistry and Biological Activities Update

et al. 2021

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The Stevia genus (Asteraceae) comprises around 230 species, distributed from the southern United States to the South American Andean region. Stevia rebaudiana, a Paraguayan herb that produces an intensely sweet diterpene glycoside called stevioside, is the most relevant member of this genus. Apart from S. rebaudiana, many other species belonging to the Stevia genus are considered medicinal and have been popularly used to treat different ailments. The members from this genus produce sesquiterpene lactones, diterpenes, longipinanes, and flavonoids as the main types of phytochemicals. Many pharmacological activities have been described for Stevia extracts and isolated compounds, antioxidant, antiparasitic, antiviral, anti-inflammatory, and antiproliferative activities being the most frequently mentioned. This review aims to present an update of the Stevia genus covering ethnobotanical aspects and traditional uses, phytochemistry, and biological activities of the extracts and isolated compounds.

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“… 7 , 8 , 9 , 10 , 11 The main cellular components of the airway are the airway epithelial cells and the airway smooth muscle cells (ASMCs). 12 Studies have shown that one of the main reasons for airway remodeling in patients with asthma is an increase in the proliferation and migration of ASMCs. 13 , 14 Several inflammatory mediators are essential for airway remodeling.…”

Section: Introductionmentioning

confidence: 99%

“… 24 Recent research has revealed that lncRNAs play a key role in airway remodeling and regulation of the proliferation and migration of ASMCs. 12 , 21 For example, lncRNA brain cytoplasmic RNA 1 (BCYRN1) promotes ASMCs proliferation and migration through the upregulation of receptor potential 1. 25 LncRNA antisense noncoding RNAs at the INK4 locus (ANRIL) have been reported to play a significant role in cancers and cardiovascular diseases.…”

Section: Introductionmentioning

confidence: 99%

“…Numerous studies have found that lncRNAs are involved in various biological activities and are tissue‐specific, suggesting that they could be potential diagnostic markers for disease 24 . Recent research has revealed that lncRNAs play a key role in airway remodeling and regulation of the proliferation and migration of ASMCs 12,21 . For example, lncRNA brain cytoplasmic RNA 1 (BCYRN1) promotes ASMCs proliferation and migration through the upregulation of receptor potential 1 25 .…”

Section: Introductionmentioning

confidence: 99%

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Long noncoding RNA antisense noncoding RNA in the INK4 locus inhibition alleviates airway remodeling in asthma through the regulation of the microRNA‐7‐5p/early growth response factor 3 axis

Wang

Liu

2023

Immunity Inflam & Disease

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Asthma, a chronic inflammatory disease of the airways, clinically manifests as airway remodeling. The purpose of this study was to probe the potential role of long noncoding RNA (lncRNA) antisense noncoding RNA in the INK4 locus (lncRNA ANRIL) in the proliferation and migration of airway smooth muscle cell (ASMC) and to explore its potential mechanisms in asthma. Serum samples were obtained from 30 healthy volunteers and 30 patients with asthma. Additionally, platelet‐derived growth factor‐BB (PDGF‐BB) was used to induce airway remodeling in ASMCs. The level of lncRNA ANRIL and microRNA (miR)‐7‐5p in serum samples were measured by quantitative reverse transcriptase polymerase chain reaction (qRT‐PCR). TargetScan predicted the binding site of miR‐7‐5p to early growth response factor 3 (EGR3) and validated the results using a dual‐luciferase reporter assay. 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyl‐2H‐tetrazolium bromide (MTT) and Transwell assays were used to detect cellular proliferation and migration, respectively. Subsequently, changes in proliferation‐ and migration‐related genes were verified using western blot analysis and qRT‐PCR. These results indicate that lncRNA ANRIL was upregulated in the serum and PDGF‐BB‐induced ASMCs of patients with asthma, whereas miR‐7‐5p expression was reduced. EGR3 was a direct target of miR‐7‐5p. LncRNA ANRIL silencing inhibited the proliferation or migration of ASMCs induced by PDGF‐BB through miR‐7‐5p upregulation. Mechanistic studies indicated that miR‐7‐5p inhibits the proliferation or migration of PDGF‐BB‐induced ASMCs by decreasing EGR3 expression. EGR3 upregulation reverses the role of miR‐7‐5p in airway remodeling. Thus, downregulation of lncRNA ANRIL inhibits airway remodeling through inhibiting the proliferation and migration of PDGF‐BB‐induced ASMCs by regulating miR‐7‐5p/EGR3 signaling.

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Eupatilin alleviates airway remodeling via regulating phenotype plasticity of airway smooth muscle cells

Cited by 8 publications

References 26 publications

Pretreatment with Eupatilin Attenuates Inflammation and Coagulation in Sepsis by Suppressing JAK2/STAT3 Signaling Pathway

Pretreatment with Eupatilin Attenuates Inflammation and Coagulation in Sepsis by Suppressing JAK2/STAT3 Signaling Pathway

Stevia Genus: Phytochemistry and Biological Activities Update

Long noncoding RNA antisense noncoding RNA in the INK4 locus inhibition alleviates airway remodeling in asthma through the regulation of the microRNA‐7‐5p/early growth response factor 3 axis

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